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K Kienast

Publications and source records attributed to K Kienast.

At least 19 recordsLinked to original sources
PubMed2000

Soot-exposed mononuclear cells increase inflammatory cytokine mRNA expression and protein secretion in cocultured bronchial epithelial cells.

BACKGROUND: Soot particles are air pollutants capable of inducing airway and lung parenchymal injury. Mononuclear and bronchial epithelial cells are central to the maintenance of homeostasis and inflammation in the airways. OBJECTIVES: The aim of this study was to evaluate the contribution of mononuclear cells to the release of inflammatory mediators by bronchial epithelial cells. METHODS: To model the in vivo situation, an in vitro system of cocultured blood monocytes and BEAS-2B cells was established in a transwell system. Blood monocytes were exposed to soot particles (FR 101) at concentrations of up to 100 microg/10(6) cells. Inflammatory cytokine mRNA and protein concentrations were quantified in BEAS-2B mono- and BEAS-2B-BM cocultures by RT-PCR and ELISA following exposure to soot for 1 and 8 h. RESULTS: No inflammatory cytokine mRNA expression was observed in unstimulated BEAS-2B cells. IL-6 and IL-8 mRNA and protein levels showed a dose-dependent elevation in FR 101-exposed blood monocytes. In addition, both IL-6 and IL-8 mRNA expression was upregulated in cocultured BEAS-2B cells while cytokine concentrations in the blood monocyte-BEAS-2B coculture medium were significantly increased. This upregulation was likely due to a synergism of two cell populations. CONCLUSIONS: Exposure to soot particles induces an autocrine stimulation of inflammatory cytokine release by blood monocytes and BEAS-2B cells. Since IL-6 and IL-8 play a major role in the pathogenesis and persistence of bronchial inflammation, these findings may serve as a partial explanation for the aggravation of asthmatic and bronchitic symptoms after exposure to soot.

Adult↗
PubMed2000

Asbestos-exposed blood monocytes--deoxyribonucleic acid strand lesions in co-cultured bronchial epithelial cells.

OBJECTIVES: In lungs of asbestos-exposed persons alveolar and interstitial macrophages are able to release genotoxic substances such as reactive oxygen intermediates. It is unknown whether reactive oxygen intermediates released by macrophages are able to induce DNA (deoxyribonucleic acid) strand lesions in neighboring bronchial epithelial cells. METHODS: A co-culture (transwell) system was established which allows exposure of human blood monocytes cultured on a polycarbonate membrane within a distance of 1 mm of a monolayer of the bronchial epithelial cell line BEAS-2B. RESULTS: Exposure of blood monocytes to chrysotile B (100 microg/10(6)cells) caused an up to 2.8-fold increase in DNA strand lesions in co-cultured BEAS-2B cells measured by alkaline elution when compared with the levels of control cells after 1, 3, 24, and 48 hours. The main DNA damage thus occurred as early as within 1 hour of incubation, corresponding to the time course of the release of reactive oxygen intermediates by blood monocytes determined by chemiluminescence. The maximum release of reactive oxygen intermediates (3.2-fold increase over control values) was measured after 30 minutes of exposure of blood monocytes to chrysotile B. The addition of catalase (200 U/ml) or desferoxamine (100 microM) to the culture medium blocked almost completely the induction of DNA strand lesions in this system (maximum 85%). CONCLUSIONS: Exposure of blood monocytes to chrysotile B results in an increase in the release of reactive oxygen intermediates and induces DNA strand lesions in neighboring bronchial epithelial cells.

Adult↗
PubMed1999

Reactive oxygen intermediate-release of fibre-exposed monocytes increases inflammatory cytokine-mRNA level, protein tyrosine kinase and NF-kappaB activity in co-cultured bronchial epithelial cells (BEAS-2B).

Some pulmonary diseases like bronchitis or asthma bronchiale are mediated by inflammatory mechanisms in bronchial epithelial cells. Alveolar macrophages are located directly in the surrounding of these cells, so that we suppose an interaction between epithelial cells and macrophages regarding to the release of inflammatory mediators. For measuring the contribution of macrophages to the release of inflammatory mediators by bronchial epithelial cells, we established an in vitro model of co-cultured blood monocytes (BM) and BEAS-2B cells in a transwell system (Costar). BM were exposed to Chrysotile B and soot particle FR 101 in a concentration of 100 microg/10(6) cells. After up to 90 min exposure time ELISA, EMSA (electromobility shift assay) and RT-PCR were used to measure protein tyrosine kinase activity, protein activity of NF-kappaB and cytokine (IL-1beta, IL-6, TNF-alpha) specific mRNA levels in BEAS-2B cells. We observed an increase in protein tyrosine kinase activity (up to 1.8 +/- 0.5-fold) and NF-kappaB protein activity in BEAS-2B cells after particle or fibre exposure of co-cultured BM. Consecutive IL-1beta-, IL-6- and TNF-alpha-mRNA were elevated (up to 1.9 +/- 0.58-fold). Protein tyrosine kinase activity, NF-kappaB activity, and the synthesis of cytokine-specific mRNA were inhibited by antioxidants. These data suggest a ROI-dependent NF-kappaB mediated transcription of inflammatory cytokines in bronchial epithelial cells.

Adult↗
PubMed1999

Additional NO2 exposure induces a decrease in cytokine specific mRNA expression and cytokine release of particle and fibre exposed human alveolar macrophages.

Soot particles, asbestos fibres and irritant gas are common air pollutants which are able to induce lung and airway pulmonary injury. The aim of this study was to investigate the effect of a simultaneous NO2 and particle or fibre exposure on the proinflammatory specific mRNA expression and protein secretion of human alveolar macrophages (AM) in comparison to only particle or fibre exposed AM. AM were simultaneously exposed to FR 101, P 90, TiO2 or Chrysotile B at a concentration of 100 microg/10(6) cells and to NO2 at a concentration of 1.0 ppm for 30 min. Particle or fibre exposure of the AM was continued in humidified air at 5% CO2 and 37 degrees C for an additional hour (harvesting of total RNA) or additional 7 hrs (harvesting of culture supernatant). The mRNA expression of the proinflammatory cytokines IL-1beta, IL-6, IL-8 and TNF-alpha of NO2-particle/fibre co-exposed AM and only particle or fibre exposed AM was detected using specific RT-PCR. IL-1beta-, IL-6-, IL-8- and TNF-alpha-specific protein secretion was measured by ELISA. Cytotoxicity was detected by lactatedehydrogenase quantification in the culture supernatant. We observed an increased IL-1beta-, IL-6-, IL-8- and TNF-alpha-specific mRNA expression of particle or fibre exposed AM, which was decreased after an additional NO2 exposure. Also the particle or fibre exposure induced significant increase in IL-1beta-, IL-6-, IL-8 and TNF-alpha-release of AM which was decreased after an additional NO2 exposure (p <0.031). The relative cytotoxicity of the NO2-particle/fibre co-exposure was higher than the particle or fibre induced cytotoxicity, but mostly <10%. Therefore it is concluded that particle or fibre exposure may result in an increase in proinflammatory cytokine release by AM, which may be decreased by toxic NO2 due to the oxidative potential (e.g. lipidperoxydation) of this irritant gas. Particle, asbestos fibre and irritant gas exposure may induce airway and pulmonary injury by the activation of AM and consecutive proinflammatory cytokine release.

Aged↗
PubMed1999

Indoor air pollutants stimulate interleukin-8-specific mRNA expression and protein secretion of alveolar macrophages.

Indoor air pollutants may cause inflammatory changes of the airways and adjacent pulmonary tissue. After phagocytosis of inhaled particles alveolar macrophages (AM) release chemotactic mediators capable of attracting inflammatory cells into the lung tissue. To evaluate these mechanisms further peripheral blood mononuclear cells (PBMNC) and human AM (freshly recovered from the lower respiratory tract) were exposed to the indoor particles Soot FR 101 and Printex 90, the asbestos fiber Chrysotile B, and titanium dioxide (TiO2) at concentrations of 10 or 50 microg/10(6) cells for up to 8 h. The migration of granulocytes into the conditioned supernatants of AM and PBMNC was quantified by chemotaxis assay in a Boyden chamber. Granulocyte migration increased by 42.3 +/- 25.8% (Chrysotile B), 64. 6 +/- 18.3% (FR 101), 74.2 +/- 16.5% (P 90), and 86.7 +/- 25.6% (TiO2) in AM-conditioned supernatants (p < 0.05). Qualitative, Interleukin (IL)-8 specific reverse transcriptase-polymerase chain reaction was performed after exposure of AM or PBMNC to Chrysotile B, FR 101, P 90, and TiO2 at concentrations of 10 and 50 microg/10(6) cells for 90 min. Each of the tested particles caused an increase in IL-8-specific mRNA expression of AM or PBMNC after particle exposure compared with the unexposed control. To find out if IL-8, the most powerful granulocyte chemokine, is involved, supernatants were preincubated with anti-IL-8. Granulocyte migration decreased by up to 35 +/- 15% (50 ng/ml anti-IL-8) and 41.5 +/- 16% (100 ng/ml anti-IL-8) (p < 0.0625) in AM-conditioned supernatants. Pretreatment of the granulocytes with human IL-8 decreased by up to 59 +/- 18% (10 ng/ml) (p < 0.0625) in AM-conditioned supernatants. Similar reaction patterns were observed using anti-IL-8-pretreated supernatants of particle-exposed PBMNC. In conclusion, indoor air pollutants may promote inflammatory changes in the lung via IL-8 release by alveolar macrophages.

Adult↗
PubMed1999

Production of reactive oxygen intermediates by human macrophages exposed to soot particles and asbestos fibers and increase in NF-kappa B p50/p105 mRNA.

Alveolar macrophages (AM) play a decisive role in the immunologic defense system of the lung and in inflammatory pulmonary pathomechanisms. AM and blood monocytes (BM) were exposed to chrysotile B, soot FR 101, and Printex 90 (P 90). We evaluated the reactive oxygen intermediate (ROI) release of AM and BM after particle exposure. ROI release was measured by chemiluminescence. Thirty-minute exposure caused a significant (up to 2.5-fold) increase in ROI release of AM (100 micrograms/10(6) cells) compared with control experiments (p < 0.01). Identical exposure conditions for BM resulted in a similar reaction pattern (maximum 2.2-fold increase in ROI release; p < 0.05). After a 90-min particle exposure at concentrations of 10 and 100 micrograms/10(6) cells, we investigated the steady-state level of p50/p105 mRNA encoding for the precursor protein of the p50 subunit of nuclear factor kappa B (NF-kappa B) by semiquantitative reverse transcription-polymerase chain reaction. One hundred micrograms Chrysotile B, FR 101, or P 90 induced a significant maximum 4.0-fold up-regulation of NF-kappa B gene expression in AM and a 3.3-fold up-regulation in BM (p < 0.05). The addition of superoxide dismutase (200 U/ml) to particle- and fiber-exposed macrophages resulted in inhibition of ROI release and a decrease in NF-kappa B mRNA expression (70%). NF-kappa B is an important transcription factor involved in the regulation of numerous genes (e.g., for inflammatory cytokines, and cytokine receptors). These cytokines are supposed to be involved in inflammatory pathomechanisms in bronchial epithelial cells, which result, for example, in chronic obstructive pulmonary disease. Our results suggest that particle-induced ROI release is associated with an increase in NF-kappa B (p50/p105) mRNA steady-state level.

Adult↗
PubMed1999

Treatment of chronic sarcoidosis with an azathioprine/prednisolone regimen.

In a few patients with chronic sarcoidosis, prolonged, unacceptably high doses of corticosteroids are required to achieve symptomatic relief. In these cases, a corticosteroid-sparing drug might be administered to allow long-term treatment without the adverse effects of corticosteroids. This study examines azathioprine as a prednisolone-sparing treatment. In an open study, the course of 11 patients with chronic sarcoidosis was analysed. In an induction phase, 2 mg azathioprine x kg body weight (BW)(-1) x day(-1) in combination with 0.6-0.8 mg prednisolone x kg BW(-1) x day(-1) were administered with prednisolone being reduced to 0.1 mg x kg BW(-1) x day(-1) within 2-3 months. This was followed by a 21-22-month maintenance phase with 2 mg azathioprine x kg BW(-1) x day(-1) and 0.1 mg prednisolone x kg BW(-1) day(-1). Clinical parameters and immunological findings of bronchoalveolar lavage (BAL) were analysed. All patients had significant symptomatic relief and improvements or resolutions of physiological, serological and radiographic findings without suffering from serious adverse effects. Nine of 11 patients completed therapy after 19-26 months, and 2/11 patients terminated therapy after 8 and 12 months, respectively. Eight patients had remissions lasting 4-73 months. Three relapses occurred after 8, 18, and 22 months. During the induction phase, BAL cell composition changed and their activity in terms of cytokine release was suppressed. This preliminary study suggests that azathioprine may be effective as a corticosteroid-sparing agent in long-term therapy of sarcoidosis, but a much larger study is necessary to give the definitive answer.

Adult↗
PubMed1998

In vitro study of human alveolar macrophages inflammatory mediator transcriptions and releases induced by soot FR 101, Printex 90, titandioxide and Chrysotile B.

Soot FR 101, Printex 90 and Chrysotile B are frequently found in indoor air pollutants phagocytized by alveolar macrophages (AM) involved in inflammatory pulmonary processes as, e.g. in cytokine secretions. The transcription factor NF-kappaB has a role in the trans-duction pathway of proinflammatory cytokines like IL-1beta, IL-6 and TNF-alpha. We therefore investigated whether the transcription factor NF-kappaB and subsequent inflammatory cytokine secretions by AM are induced by exposure to these particles compared to the inert TiO2. AM were incubated for 90 min at particle concentrations of up to 100 microg/10(6) cells. Sequential reverse transcription and semiquantitative cDNA amplification (RT-PCR) was used to measure NF-kappaB and cytokine mRNA expressions. Compared to control exposures these particles induced an up to 4.6-fold increase in gene expression of the transcription factor NF-kappaB (p < 0.01), resulting in up to 12.9-fold enhanced transcription rates of IL-1beta, IL-6 and TNF-alpha (p <0.05). The particles and fibre dependent increases in mRNA reached maximum levels at 90 min post exposure. After an exposure time of 8 hrs, IL-1beta, IL-6 and TNF-alpha proteins, measured by enzyme-linked immunosorbent assays (ELISA), were significant elevated in supernatants of AM, revealing an up to 30.5-fold increase in TNF-alpha secretion rates (p <0.01). Our results suggest that exposure of human AM to soot FR 101, Printex 90, TiO2 and Chrysotile B induce the transcription and production of proinflammatory cytokines via NF-kappaB and may play an important role in the pathogenesis of airway disease and lung parenchymal injury.

Asbestos, Serpentine↗
PubMed1998

[A new method for imaging ventilation-distribution with 3Helium in magnetic resonance tomography].

BACKGROUND: Conventional 1H-MRI of the lung is restricted by susceptibility effects and low proton density: Recently, imaging of lung ventilation in MRI has become feasible using hyperpolarised inert gases with a spin of I = 1/2, such as 3He and 129Xe, as inhalative "contrast agents". New technical developments, preclinical and clinical application of this method are described. MATERIALS AND METHODS: With optical laser pumping high polarisation rates can be achieved, resulting in a high signal-to-noise ratio (S/N). A dedicated application system allows accurate administration of 3He boli at different time points during inspiration. Thus, dynamic ventilation imaging becomes possible. Prerequisites for this method include a dedicated coil as well as a spectroscopy option at the MRI system. Fast sequences and low flip angles are employed to comply with the relaxation of hyperpolarise 3He in vivo. RESULTS: Overall homogeneous signal intensity (SI) represents physiological conditions. Obstructive lung disease is associated with generalised or localised signal inhomogeneity. Different time constants of specific lung regions are probably responsible for this kind of inhomogeneous inspiratory distribution of ventilation. Tumours show a clear ventilation deficit, correlating with non-ventilated lung areas. CONCLUSION: 3He MRI is a promising new modality for the evaluation of ventilation distribution under different pathological conditions. This may include obstructive lung disease and assessment of ventilation distribution before and after thoracic surgery. Furthermore, evaluation of patients with acute lung failure and validation of ventilator settings in anaesthesia may be performed.

Contrast Media↗
PubMed1997

Reduction of cytokine release of blood and bronchoalveolar mononuclear cells by ambroxol.

Ambroxol is a mucolytic agent frequently used in the treatment of chronic bronchitis. It has been reported, following clinical and in-vitro studies, that ambroxol exhibits an anti-inflammatory action. This capability was investigated by activating bronchoalveolar lavage cells and peripheral blood mononuclear cells in-vitro to elicit the release of tumor necrosis factor alpha, interleukin-2 and interferon gamma, whilst simultaneously exposing them to varying pharmacological concentrations of ambroxol (10, 1, and 0.1 microM). After 24 h it was observed that the isolated tissue-culture supernatants showed a dose-dependent reduction in the concentration of the tested cytokines; 10 microM (12 to 37% reduction) and 1 microM to (6 to 27% reduction). At 0.1 microM, a significant reduction could only be observed in the release of interleukin-2 by bronchoalveolar lavage cells. These results demonstrate, that ambroxol exhibits anti-inflammatory actions in concentrations achievable in vivo.

Ambroxol↗
PubMed1997

[Ileus caused by tuberculosis].

We report on a 30-year old patient suffering from acute abdomen. X-ray examinations (abdomen photograph, passage of contrast medium) showed an obstructive ileus of the small bowel. Exploratory laparatomy revealed an obstruction of the small bowel by means of masses of lymphatic nodes as part of a mesenteric lymphadenopathy. M. tuberculosis was identified as growing in cultures of peritoneal smears and material of lymphatic nodes. The retrospective examination of the pre-operative x-ray photographs of the chest showed an old primary complex of the lung. A combination of four antituberculotic drugs: Rifampicin, ethambutol, isoniazid and pyrazinamid was administered following the concept of a 6-month regimen. This treatment was successful: CT-scans of the abdomen showed a reduction of the mesenterial lymphadenopathy and the disappearance of the duodenal impression in the follow-up after 4 weeks of therapy. The abdominal TBC represents a severe disease requiring a differential diagnostic distinction from other abdominal diseases such as ileitis terminalis, Crohn's disease, neoplass as especially gastrointestinal lymphomas, giardiasis, amoebiasis and yersinia enterocolitis. The disease has a special importance among immigrant populations.

Abdomen, Acute↗
PubMed1996

Combined exposures of human ciliated cells to different concentrations of sulfur dioxide and nitrogen dioxide.

In the present study we investigated the influence of two common air pollutants, sulfur dioxide (SO2) and nitrogen dioxide (NO2) on ciliary beat frequency (CBF). Ciliated cells were obtained by nose brush from 12 healthy volunteers and placed on a polycarbonate membrane which was in contact with Ringer's electrolyte solution. This allowed the supply of the cells by capillarity in parallel to the reaction of the pollutants with the cell surfaces. In an exposure chamber the cells were exposed for 30 min. at 37 degrees C either to SO2 (2.5-12.5 ppm) or to NO2 (3.0-15.0 ppm), or to a mixture of NO2 (12.0 ppm) and SO2 (2.5 or 5.0 ppm). CBF was measured by video-interference-microscopy. With SO2 we observed a dose-dependent decrease in CBF with Ringer's solution. 2.5 ppm SO2 caused a 42.8% decrease and 12.5 ppm a decline of approximately 100% (8.10 +/- 0.24 Hz vs. 0.28 +/- 0.20 Hz). In parallel, we observed a decrease in the pH-value from 7.4 to 3.6. 30 min. NO2 exposure (3.0-15.0 ppm) induced a significant dose dependent increase in CBF from 8.4 +/- 0.34 Hz to 9.4 +/- 0.44 Hz. Exposure to a mixture of SO2 and NO2 with Ringer's solution revealed that SO2 exerts a stronger influence on CBF than NO2. Exposure to both pollutants resulted in the same as exposure to SO2 alone. Our findings demonstrate a strong correlation between SO2-modified pH values and CBF. Exposure to a combination of two pollutants revealed the dominant influence of SO2 on CBF while the augmented effect of exposure to NO2 alone might be due to the oxidative potential of this gas.

Adult↗
PubMed1996

Modulation of TNF-alpha secretions by alveolar macrophages and blood monocytes after soot-particle or asbestos fibre exposure.

Activated monocytes secrete tumor necrosis factor-alpha (TNF-alpha), whose inflammatory and fibroblast activating characteristics may play a role in the maintenance of pulmonary inflammatory processes and subsequent fibrosis. Human alveolar macrophages (AM) and peripheral blood mononuclear cells (PBMNC) were exposed to soot particles or asbestos fibres in concentrations ranging from 5-50 micrograms/1 x 10(6) cells for 8 hrs in RPMI medium. A culture was established with the exposed monocytes and the remaining cells were used to determine TNF-alpha. TNF-alpha was quantified by commercial ELISA-kits. 8 hrs exposure to soot particles and asbestos fibres induced a significant increase in spontaneous TNF-alpha release (p < 0.05). Cytotoxicity of monocytes was checked by trypan blue exclusion and lactate dehydrogenase assay, noted values ranging from 0.5%-16.2%.

Asbestos↗
PubMed1996

Modulation of IL-1 beta, IL-6, IL-8, TNF-alpha, and TGF-beta secretions by alveolar macrophages under NO2 exposure.

Activated alveolar macrophages (AMs) secrete interleukine (IL)-1 beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta (TGF-beta), whose inflammatory and fibroblast-activating characteristics may play a role in the maintenance of pulmonary inflammatory processes and subsequent fibrosis. Human AMs were transferred to a gas cylinder and exposed to NO2 in concentrations ranging from 0.1 to 0.5 ppm in synthetic air for 30 min at 37 degree C. AMs were fixed on a polycarbonate membrane and placed on culture medium. A culture was established, with the exposed AM (nonstimulated or stimulated with 1 microgram/ml lipopolysaccharide [LPS]), and the remaining cells were used to determine the cytokines. IL-1 beta, IL-6, and IL-8 were quantified by commercial enzyme-linked immunosorbent assay kits (ELISA kits). TNF-alpha was determined with a "sandwich" ELISA, using the biotin-streptavidin system. NO2 exposure of nonstimulated AM did not result in changes in IL-1 beta, IL-6, TNF-alpha, and TGF-beta release, compared to the situation with control experiments. Exposure for 30 min to NO2 induced a significant decrease of LPS-stimulated IL-1 Beta, IL-6, IL-8, and TNF-alpha (p < .05). The release of TGF-beta was not significantly affected by NO2 exposure. Cytotoxicity of AM was checked by trypan blue exclusion, with values ranging from 1.3 to 3.0%. NO2 exposure of LPS-stimulated AM resulted in a functional impairment of AM after NO2 exposure regarding IL-1 beta, IL-6, IL-8, and TNF-alpha. Neither the spontaneous nor the stimulated release of TGF-beta were influenced by NO2.

Bronchoalveolar Lavage Fluid↗
PubMed1996

Spontaneous interleukin 2 release of bronchoalveolar lavage cells in sarcoidosis is a codeterminator of prognosis.

There is mounting evidence that activated interleukin 2 (IL-2)-releasing lymphocytes play a central role in the immunopathogenesis of sarcoidosis by directing inflammatory reactions and granuloma formation. In the context that a significant proportion of these cells accumulates in the lung and releases mediators, we hypothesized that different immunologically defined stages of sarcoidosis can be identified. A cohort of 89 sarcoidosis patients was allocated to four groups according to the following criteria: stage A, a low number of bronchoalveolar lavage (BAL) lymphocytes (< 20%) without IL-2 release (< 1 unit/ml in BAL cell culture supernatant); stage B, BAL lymphocytes < 20%, with IL-2 release (> or = 1 unit/ml); stage C, BAL lymphocytes > or = 20% with IL-2 release; and stage D, > or = 20% BAL lymphocytes without IL-2 release. Although patients of stages C and D (n = 49) exhibited lymphocytic inflammation, only 20/49 of these patients had activated IL-2-releasing alveolar lymphocytes. BAL of groups A and B showed a low number of lymphocytes, but the lymphocytes were activated in 20/40 patients. Forty-four patients not receiving therapy were reevaluated by pulmonary function tests 8 +/- 1 months after BAL. Progressive disease was found in 9/12 patients of group C and stable or regressing disease in 13/13 patients of group A. These results demonstrate that a combination of BAL parameters can yield prognostic information.

Adult↗
PubMed1996

Chemotactic response of human alveolar macrophages and blood monocytes elicited by exposure to sulfur dioxide.

An experimental study was undertaken to investigate the in vitro effect of sulfur dioxide on the chemotactic activity of alveolar macrophages (AM) and blood monocytes (BM). The cells were placed on a polycarbonate membrane and exposed to SO2 0.5, 1.5 and 2.5 ppm for 15 min. Control experiments were performed with exposure of the cells to synthetic air with 5% CO2. After gas exposure the cells were incubated with the chemotactic active agent C5a in 5% carbon dioxide (CO2) at 37 degrees C for 60 min. The numbers of AM and BM passing actively through the membrane were quantified using light microscopy. Our results show a dose-dependent reduction in the migration rate of cells under SO2 exposure. SO2 0.5 ppm induced a 29% and SO2 2.5 ppm a 53% decrease in migration of AM compared with the control exposure to synthetic air (P < 0.01). Identical experiments with BM resulted in a decrease in migration of up to 57% (P < 0.01). At SO2 concentrations of up to 2.5 ppm no significant cytotoxic effects were observed for AM or BM. The data demonstrate that exposure to SO2 may reduce the chemotactic activity of AM and BM. Our results further suggest that the decrease in cell migration induced by SO2 is due to changes in chemotactic mechanisms and not to cell death.

Aged↗
PubMed1996

Regulation of immunomodulatory functions by granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in vivo.

The present study was designed to investigate in vivo immunomodulatory properties of hematopoietic growth factors. The influence on the activation of cytokine synthesis and on the expression of surface antigens associated with cellular activation of G-CSF or GM-CSF was investigated in cancer patients receiving these factors. One single dose of growth factor was administered to patients with bladder cancer (G-CSF group) or small cell lung cancer (GM-CSF group) before chemotherapy. After cytoreductive chemotherapy patients received supportive therapy with G-CSF or GM-CSF. Peripheral blood mononuclear cells and plasma samples were obtained for flow cytometry, Northern blot analysis, and assessment of cytokine protein levels after single-dose as well as after continuous cytokine administration. Our results demonstrate differences in the induction of biological activities by GM-CSF and G-CSF in vivo which correlate well with in vitro findings. Among mature hematopoietic cells the effect of G-CSF is restricted to the granulocyte lineage. With GM-CSF moderate but unequivocal modulation of monocyte function was observed. On peripheral blood monocytes expression of MHC class-II molecules and CD44 was markedly stimulated. After one single dose of GM-CSF, plasma levels of sCD25 and IL-1RA were significantly induced (p < 0.0001, p = 0.032, respectively) and a trend to increased IL-8 levels was observed. The changes in plasma proteins were not correlated with shifts of mRNA expression for IL-8 and IL-1RA. T-cell activation was not observed with either cytokine. These results suggest that immunomodulatory features are differentially regulated by G-CSF and GM-CSF. The clinical relevance of a selective use of both hematopoietic growth factors in various disease settings remains to be determined.

Adjuvants, Immunologic↗